Download PDF
Synthesis 2009(5): 741-754  
DOI: 10.1055/s-0028-1083360
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Diastereoselective Synthesis of γ-Amino Acids and Their Derivatives from Nitroethane via Intermediacy of 5,6-Dihydro-4H-1,2-oxazines Bearing the CH2CH(CO2Me)2 Substituent at C3

Alexey Yu. Sukhorukov, Alexey V. Lesiv, Yulia A. Khomutova, Sema L. Ioffe*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russian Federation
Fax: +7(499)1355328; e-Mail: iof@ioc.ac.ru;
Further Information

Publication History

Received 14 October 2008
Publication Date:
11 February 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Stereoselective two-step reduction of available 2-[(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates provides an efficient route to derivatives of different γ-amino acids. The mechanism and stereochemistry of the first step, reduction of the C=N bond with sodium cyanoborohydride, is discussed.

Key words

5,6-dihydro-4H-1,2-oxazines - reduction - γ-amino acids - oxyiminium cations

    References

  • 1a Hipelli C. Reissig H.-U. Liebigs Ann. Chem.  1990,  475 
    Google Scholar
  • 1b Paulini K. Gerold A. Reissig H.-U. Liebigs Ann. Chem.  1995,  667 
    Google Scholar
  • 1c Angermann J. Homann K. Reissig H.-U. Zimmer R. Synlett  1995,  1014 
    Google Scholar
  • 1d Zimmer R. Collas M. Czerwonka R. Hain U. Reissig H.-U. Synthesis  2008,  237 
    Google Scholar
  • 2a Hippeli C. Zimmer R. Reissig H.-U. Liebigs Ann. Chem.  1990,  469 
    Google Scholar
  • 2b Nakanishi S. Otsuji Y. Itoh K. Hayashi N. Bull. Chem. Soc. Jpn.  1990,  63:  3595 
    Google Scholar
  • 2c Nakanishi S. Shirai Y. Takahashi K. Otsuji Y. Chem. Lett.  1981,  869 
    Google Scholar
  • 3 Chrystal EJT. Gilchrist TL. Stretch W. J. Chem. Res., Synop.  1987,  180 ; J. Chem. Res., Miniprint 1987, 1563
    Google Scholar
  • 4 Zimmer R. Collas M. Roth M. Reissig H.-U. Liebigs Ann. Chem.  1992,  709 
    CrossrefGoogle Scholar
  • 5a Sukhorukov AY. Lesiv AV. Eliseev OL. Khomutova YuA. Bondarenko TN. Lapidus AL. Ioffe SL. Mendeleev Commun.  2007,  122 
    Google Scholar
  • 5b Sukhorukov AY. Lesiv AV. Khomutova YuA. Ioffe SL. Nelyubina YV. Synthesis  2008,  1205 
    Google Scholar
  • 5c Sukhorukov AY. Lesiv AV. Eliseev OL. Khomutova YuA. Ioffe SL. Borissova AO. Eur. J. Org. Chem.  2008,  4025 
    Google Scholar
  • 6a Henning R. Lerch U. Urbah H. Synthesis  1989,  265 
    Google Scholar
  • 6b Gallos JK. Sarli VC. Massen ZS. Varvogli AC. Papadoyanni CZ. Papaspyrou SD. Argyropoulos NG. Tetrahedron  2005,  61:  565 
    Google Scholar
  • 7 Tishkov AA. Reissig H.-U. Ioffe SL. Synlett  2002,  863 
    Article in Thieme ConnectGoogle Scholar
  • 8 Lyapkalo IM. Ioffe SL. Russ. Chem. Rev. (Engl. Transl.)  1998,  67:  467 
    CrossrefGoogle Scholar
  • 9a Sukhorukov AY. Klenov MS. Ivashkin PE. Lesiv AV. Khomutova YuA. Ioffe SL. Synthesis  2007,  97 
    Google Scholar
  • 9b Klenov MS. Lesiv AV. Khomutova YuA. Nesterov ID. Ioffe SL. Synthesis  2004,  1159 
    Google Scholar
  • 9c Eliseev OL. Ivashkin PE. Ostapenko AG. Lesiv AV. Khomutova YuA. Ioffe SL. Lapidus AL. Synlett  2006,  2239 
    Google Scholar
  • 10 Zimmer R. Arnold T. Homann K. Reissig H.-U. Synthesis  1994,  1050 
    Article in Thieme ConnectGoogle Scholar
  • 11 Ivashkin PE. Sukhorukov AY. Eliseev OL. Lesiv AV. Khomutova YuA. Ioffe SL. Synthesis  2007,  3461 
    Article in Thieme ConnectGoogle Scholar
  • 17a Ben-Ishai D. Altman J. Peled N. Tetrahedron  1977,  33:  2715 
    Google Scholar
  • 17b Ohkuma T. Ishii D. Takeno H. Noyori R. J. Am. Chem. Soc.  2000,  122:  6510 
    Google Scholar
  • 17c Lauer WM. Lockwood RG. J. Am. Chem. Soc.  1954,  76:  3974 
    Google Scholar
  • 17d Boger DL. Machiya K. J. Am. Chem. Soc.  1992,  114:  10056 
    Google Scholar
  • 17e Gutzwiller J. Uskokovic M. J. Am. Chem. Soc.  1970,  92:  204 
    Google Scholar
  • 19 Buchholz M. Reissig H.-U. Eur. J. Org. Chem.  2003,  3524 
    CrossrefGoogle Scholar
  • 20 Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
    CrossrefPubMedGoogle Scholar
  • 21 Lambert JB. Takeuchi Y. Cyclic Organonitrogen Stereodynamics   VCH; New York: 1992.  Chap 7.1.1 and 7.2.1. and references cited therein
    Google Scholar
  • 22 Nesterov ID. Lesiv AV. Ioffe SL. Antpin MYu. Mendeleev Commun.  2004,  280 
    CrossrefGoogle Scholar
  • 23a Smirnov VO. Ioffe SL. Tishkov AA. Khomutova YuA. Nesterov ID. Antpin MYu. Smit WA. Tartakovsky VA. J. Org. Chem.  2004,  69:  8485 
    Google Scholar
  • 23b Khomutova YuA. Smirnov VO. Mayr H. Ioffe SL. J. Org. Chem.  2007,  72:  9134 
    Google Scholar
  • 27a Ponomarev AA. Noritsina MV. Krivenko AP. Chem. Heterocycl. Compd. (Engl. Transl.)  1970,  978 
    Google Scholar
  • 27b Fulep GH. Hoesl CE. Hofner G. Wanner KT. Eur. J. Med. Chem.  2006,  41:  809 
    Google Scholar
  • 27c Vara Prasad JVN. Loo JA. Boyer FE. Stier MA. Gogliotti RD. Turner WJ. Harvey PJ. Kramer MR. Mack DP. Scholten JD. Gracheck SJ. Domagala JM. Bioorg. Med. Chem.  1998,  6:  1707 
    Google Scholar
  • 28 Gottlieb HE. Kotlyar V. Nudelman A. J. Org. Chem.  1997,  62:  7512 
    CrossrefPubMedGoogle Scholar
12

Our attempts to reduce the N-O bond [H2 (75 bar), Raney nickel, 100 ˚C; H2 (60 bar), 5% Pd/C, 100 ˚C; SmI2, THF; COCl2, NaBH4, MeOH] in products 10 failed, therefore they could not be used in route c (Scheme  [³] ).

13

We were unable to obtain derivatives of 6 with carbamate-type protecting groups (Boc, Cbz), which are more easily cleaved, because under the applied reduction conditions tetrahydrooxazines 6 reacted neither with Boc2O nor with CbzCl.

14

Attempts to reduce this substrate with Et3SiH in TFA or TfOH; NaBH4/AcOH; and Zn/AcOH were also unsuccessful: either no conversion of the starting material was observed or protonation of oxazine leading to the corresponding salt occurred (for details see the discussion of process 4, NaBH3CN, AcOH, Scheme  [9] ).

15

Successful transformation 6h to 10h can be realized only by heating 6h in AcOH (see experimental part).

16

For similar processes in the hydrogenation of other 6-phenyl-substituted 5,6-dihydro-4H-1,2-oxazines see ref. 3.

18

Reduction of iminium salt 15c to tetrahydrooxazine 6c is accompanied by the partial formation of oxime ether 4c (yield: 25%).

24

It is noteworthy, that according to NMR cation 15c and its precursor, dihydrooxazine 4c, have the same dominant conformation.

25

In the studies²³ the stereochemistry of C-C coupling with six-membered cyclic nitronates possessing substitution at C5 was not examined. The stereochemical course the reduction of some 5-substituted dihydrooxazines with NaBH3CN¹0 can be also rationalized in terms of proximal approach of the reducing agent to the cation intermediate.

26

An example of such a process is discussed in ref. 23a.